tbuckley/cabot-search huggingface dataset:
Enhanced osseointegration of drug eluting nanotubular dental implants: An in vitro and in vivo study
Authors: Pankaj Chauhan, Alok Srivastava, Pooja Bhati, Manish Chaturvedi, Vinay Patil, Sriram Kunnoth, Nisha Kumari, Vedpal Arya, Madhur Pandya, Mohit Agarwal, Smiti Bhardwaj, Farrukh Faraz, Sanjay Chauhan, Mahesh Verma, Veena Koul, Naresh Bhatnagar
Journal: Bioactive Materials (2023)

Faster and predictable osseointegration is crucial for the success of dental implants, especially in patients with compromised local or systemic conditions. Despite various surface modifications on the commercially available Titanium (Ti) dental implants, the bioactivity of Ti is still low. Thus, to achieve both biological and therapeutic activity on titanium surfaces, surface modification techniques such as titanium nanotubes have been studied as nanotube surfaces can hold therapeutic drugs and molecules. The main aim of the present research work is to study the early osseointegration around the novel Simvastatin drug eluting nanotubular dental implant. In the present research, the titanium nanotubes were fabricated on the screw-shaped dental implant surface and the Simvastatin drug was loaded into the nanotubes using the ultrasonication dip method. In vitro and In vivo studies were carried out on the modified dental implants. In vitro cell culture study reported enhanced osteogenic activity on the drug-loaded nanotube surface implants. The invivo animal studies were evaluated by micro-CT, histopathology, and reverse torque removal analysis methods. The test results showed faster osseointegration with the strong interface on the Simvastatin drug-loaded implant surface at 4 weeks of healing as compared to the control implants.
Intracranial bleeding in acute promyelocytic leukemia treated with arsenic trioxide based regimens is associated with induction mortality but not with relapse
Authors: Uday Prakash Kulkarni, Sushil Selvarajan, N. A. Fouzia, Sharon Lionel, Sukesh Chandran Nair, Poonkuzhali Balasubramanian, Thenmozhi Mani, Aby Abraham, Biju George, Vikram Mathews
Journal: Blood Cancer Journal (2023)

Intracranial bleeding in acute promyelocytic leukemia treated with arsenic trioxide based regimens is
Distinct roles of IL-18 and IL-1β in murine model of macrophage activation syndrome
Authors: Mao Mizuta, Natsumi Inoue, Masaki Shimizu, Naoto Sakumura, Tadafumi Yokoyama, Rie Kuroda, Yasuhiro Ikawa, Naotoshi Sugimoto, Kenichi Harada, Akihiro Yachie, Taizo Wada
Journal: Journal of Allergy and Clinical Immunology (2023)
(V)aperçu on the harm of nicotine e-cigarettes
Authors: Wolfgang M. Kuebler
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>Nicotine vaping is associated with acute and chronic lung cellular, structural and functional changes that can be expected to have significant short- and long-term consequences for consumers' respiratory health</b> https://bit.ly/3MO23EV
Prematurity-related chronic respiratory disease across the life course
Authors: Liesbeth Duijts
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>Being born preterm, either extreme or late preterm, has adverse implications for respiratory health across the life course. Both child and adult respiratory physicians should raise their awareness of prematurity-related chronic respiratory disease.</b>https://bit.ly/3IW95pW
Preliminary antitumor activity of the combination of COM701 + BMS-986207 + nivolumab in patients with recurrent, metastatic MSS endometrial cancer.
Authors: Drew W. Rasco, Daniel A. Vaena, Gini F. Fleming, Ecaterina Elena Dumbrava, Oladapo O. Yeku, Manish Sharma, Kyriakos P. Papadopoulos, Ryan J. Sullivan, Stephanie Gaillard, Adeboye H. Adewoye, John William Moroney
Journal: Journal of Clinical Oncology (2023)

5595 Background: There is a high unmet medical need for the treatment of patients [pts] with microsatellite stable [MSS], recurrent, metastatic, endometrial cancer [EC]. We reported encouraging preliminary antitumor activity with the triple combination of COM701 + BMS-986207 + nivolumab in patients with platinum resistant epithelial ovarian cancer [1]. COM701 is a novel, 1st-in-class immune checkpoint inhibitor [ICI] that binds to PVRIG, a DNAM-1 axis member, leading to activation of T-and NK-cells; BMS-986207 is an ICI of TIGIT. Nivolumab is an ICI of PD-1. We hypothesized that in pts with EC, the triple combination would demonstrate antitumor activity with a favorable safety and tolerability profile. We present encouraging preliminary results. Methods: As part of an expansion cohort, we enrolled 9 patients [pts] with EC. All pts received COM701 20 mg/kg + BMS-986207 480 mg + nivolumab 480 mg all IV Q4W. Primary objectives were safety/tolerability, with secondary objective of antitumor activity in pts with EC. Key inclusion criteria: Age ≥ 18 yrs, measurable disease, MSS by IHC or genomic testing, ≤2 prior systemic cytotoxic therapies, prior PD-1/PD-L1 permissible. Key exclusion criteria: prior receipt of anti-PVRIG, anti-TIGIT. Investigator assessed responses were per RECIST v1.1, safety per CTCAE v5.0. Results: Median age 71yrs, median of 2 prior lines of therapy, prior PD-1/PD-L1 3/9 [33%]. All pts received prior cytotoxic therapy. Objective response rate (ORR) 2/9 [22%] pts; 2 pts with SD. Disease control rate [CR + PR + SD] 4/9 [44%]. There were 2 pts with confirmed PR; 1 of these pts was refractory to prior receipt of lenvatinib + pembrolizumab [best response assessment of progressive disease]. Treatment related AEs were reported in 6/9 [67%] pts, the majority 4/6 [67%] were Grade 1 [1 pt each with chills, pyrexia, back pain and pruritus, lipase increased]. No new safety signals are reported. Conclusions: The combination of COM701 + BMS-986207 + nivolumab demonstrates encouraging preliminary signal of antitumor activity in pts with EC including in a pt refractory to prior exposure to lenvatinib + pembrolizumab. The triplet combination has a favorable safety/tolerability profile. Additional data analyses and pt follow up are ongoing and will be presented at the conference. Data extract 01/24/2023. 1. Moroney JW, Yeku O et al. Triple blockade of the DNAM-axis with COM701 + BMS-986207 + nivolumab demonstrates preliminary antitumor activity in patients with platinum resistant OVCA. Annals of Oncology (2022) 16 (suppl_1): 100104-100104. 10.1016/iotech/iotech100104. Clinical trial information: NCT04570839 .
Elevated NOX4 promotes tumorigenesis and acquired EGFR-TKIs resistance via enhancing IL-8/PD-L1 signaling in NSCLC
Authors: Wen-Jing Liu, Lin Wang, Feng-Mei Zhou, Shu-Wen Liu, Wei Wang, Er-Jiang Zhao, Quan-Jun Yao, Wei Li, Yan-Qiu Zhao, Zhi Shi, Jian-Ge Qiu, Bing-Hua Jiang
Journal: Drug Resistance Updates (2023)

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been widely used for human non-small-cell lung cancer (NSCLC) treatment. However, acquired resistance to EGFR-TKIs is the major barrier of treatment success, and new resistance mechanism remains to be elucidated. In this study, we found that elevated NADPH oxidase 4 (NOX4) expression was associated with acquired EGFR-TKIs resistance. Gefitinib is the first-generation FDA-approved EGFR-TKI, and osimertinib is the third-generation FDA-approved EGFR-TKI. We demonstrated that NOX4 knockdown in the EGFR-TKI resistant cells enabled the cells to become sensitive to gefitinib and osimertinib treatment, while forced expression of NOX4 in the sensitive parental cells was sufficient to induce resistance to gefitinib and osimertinib in the cells. To elucidate the mechanism of NOX4 upregulation in increasing TKIs resistance, we found that knockdown of NOX4 significantly down-regulated the expression of transcription factor YY1. YY1 bound directly to the promoter region of IL-8 to transcriptionally activate IL-8 expression. Interestingly, knockdown of NOX4 and IL-8 decreased programmed death ligand 1 (PD-L1) expression, which provide new insight on TKIs resistance and immune escape. We found that patients with higher NOX4 and IL-8 expression levels showed a shorter survival time compared to those with lower NOX4 and IL-8 expression levels in response to the anti-PD-L1 therapy. Knockdown of NOX4, YY1 or IL-8 alone inhibited angiogenesis and tumor growth. Furthermore, the combination of NOX4 inhibitor GKT137831 and gefitinib had synergistic effect to inhibit cell proliferation and tumor growth and to increase cellular apoptosis. These findings demonstrated that NOX4 and YY1 were essential for mediating the acquired EGFR-TKIs resistance. IL-8 and PD-L1 are two downstream targets of NOX4 to regulate TKIs resistance and immunotherapy. These molecules may be used as potential new biomarkers and therapeutic targets for overcoming TKIs resistance in the future.
Antiandrogen treatment induces stromal cell reprogramming to promote castration resistance in prostate cancer
Authors: Hanling Wang, Ni Li, Qiuli Liu, Jiacheng Guo, Qiang Pan, Bisheng Cheng, Junyu Xu, Baijun Dong, Guanjie Yang, Bin Yang, Xuege Wang, Yongqiang Gu, Guoying Zhang, Yannan Lian, Wei Zhang, Mingyu Zhang, Tianyi Li, Yi Zang, Minjia Tan, Qintong Li, Xiaoming Wang, Zhengquan Yu, Jun Jiang, Hai Huang, Jun Qin
Journal: Cancer Cell (2023)
An integrated cellular and molecular model of gastric neuroendocrine cancer evolution highlights therapeutic targets
Authors: Joscha Griger, Sebastian A. Widholz, Moritz Jesinghaus, Niklas de Andrade Krätzig, Sebastian Lange, Thomas Engleitner, Juan José Montero, Ekaterina Zhigalova, Rupert Öllinger, Veveeyan Suresh, Wiebke Winkler, Svenja Lier, Olga Baranov, Riccardo Trozzo, Najib Ben Khaled, Shounak Chakraborty, Jiakun Yu, Björn Konukiewitz, Katja Steiger, Nicole Pfarr, Ashish Rajput, David Sailer, Gisela Keller, Peter Schirmacher, Christoph Röcken, Klaus W. Fagerstedt, Julia Mayerle, Marc Schmidt-Supprian, Günter Schneider, Wilko Weichert, Dinis P. Calado, Thomas Sommermann, Günter Klöppel, Klaus Rajewsky, Dieter Saur, Roland Rad
Journal: Cancer Cell (2023)
Safety and clinical activity of autologous RNA chimeric antigen receptor T-cell therapy in myasthenia gravis (MG-001): a prospective, multicentre, open-label, non-randomised phase 1b/2a study
Authors: Volkan Granit, Michael Benatar, Metin Kurtoglu, Miloš D Miljković, Nizar Chahin, Gregory Sahagian, Marc H Feinberg, Adam Slansky, Tuan Vu, Christopher M Jewell, Michael S Singer, Murat V Kalayoglu, James F Howard, Tahseen Mozaffar, Volkan Granit, Michael Benatar, Tahseen Mozaffar, Nizar Chahin, James F. Howard, Adam D. Slansky, Marc H. Feinberg, Gregory Sahagian, Tuan Vu, Denise Pereira, Julie Steele, Maria Elena Paredes, Cara Benjamin, Krishna Komanduri, Ali Aamer Habib, Julia Kimberly Fong, Luis De La Cruz, Diana Dimitrova, Manisha Chopra, Kelly Holley, Gabrielle DeMaria, April Tenorio, Naraly Requena, Beverly Mackanzie Brooks, Niraja Suresh, Jerrica Farias, Miloš D Miljković, Metin Kurtoglu, Minhtran Ngo Casi, Adam Chowdhury, Hafsa Kamboh, C Andrew Stewart, Mehmet Tosun, Yufei Shan, Shaji Daniel, Matthew T. Duvernay, Maria Kireeva, Emily English, Christopher M. Jewell, Michael S Singer, Murat V Kalayoglu
Journal: The Lancet Neurology (2023)
Silicosis and tuberculosis: A systematic review and meta-analysis
Authors: P. Jamshidi, B. Danaei, M. Arbabi, B. Mohammadzadeh, F. Khelghati, A. Akbari Aghababa, A. Nayebzade, A.H. Shahidi Bonjar, R. Centis, G. Sotgiu, M.J. Nasiri, G.B. Migliori
Journal: Pulmonology (2023)

Silicosis mostly happens in workers with high silica exposure and may accompany the development of various diseases like tuberculosis, cancer, or autoimmune diseases. The term silico-tuberculosis describes a condition in which an individual is affected by both silicosis and tuberculosis at the same time. This systematic review and meta-analysis study was conducted to evaluate the risk of tuberculosis in silicosis patients and individuals exposed to silica dust. We performed a systematic search for relevant studies up to 6 September 2022 using PubMed/ Medline, and Embase with the following keywords in titles or abstracts: "silicosis" OR "silicoses" OR "pneumoconiosis" OR "pneumoconioses" AND "tuberculosis". Cohort and case-control studies containing relevant and original information about tuberculosis infection in silicosis patients were included for further analysis. Pooled estimates and 95% confidence intervals (CI) for the relative risk of tuberculosis in individuals with silicosis compared to those without; these were evaluated using the random effects model due to the estimated heterogeneity of the true effect sizes. Out of 5352 potentially relevant articles, 7 studies were eligible for systematic review, of which 4 cohort studies were included for meta-analysis. The total population of all studies was 5884, and 90.63% were male. The mean age of participants was 47.7 years. Our meta-analysis revealed a pooled risk ratio of 1.35 (95%CI 1.18-1.53, I 2: 94.30%) which means an increased risk of silicosis patients and silica-exposed individuals to tuberculosis infection. Silicosis and silica dust exposure increase the risk of tuberculosis. Therefore, we suggest that individuals with long-time silica exposure, like mine workers, be routinely considered for both silicosis and tuberculosis screening programs.
A biomimetic liver cancer on-a-chip reveals a critical role of LIPOCALIN-2 in promoting hepatocellular carcinoma progression
Authors: Peiliang Shen, Yuanyuan Jia, Weijia Zhou, Weiwei Zheng, Yueyao Wu, Suchen Qu, Shiyu Du, Siliang Wang, Huilian Shi, Jia Sun, Xin Han
Journal: Acta Pharmaceutica Sinica B (2023)

Hepatic stellate cells (HSCs) represent a significant component of hepatocellular carcinoma (HCC) microenvironments which play a critical role in tumor progression and drug resistance. Tumor-on-a-chip technology has provided a powerful in vitro platform to investigate the crosstalk between activated HSCs and HCC cells by mimicking physiological architecture with precise spatiotemporal control. Here we developed a tri-cell culture microfluidic chip to evaluate the impact of HSCs on HCC progression. On-chip analysis revealed activated HSCs contributed to endothelial invasion, HCC drug resistance and natural killer (NK) cell exhaustion. Cytokine array and RNA sequencing analysis were combined to indicate the iron-binding protein LIPOCALIN-2 (LCN-2) as a key factor in remodeling tumor microenvironments in the HCC-on-a-chip. LCN-2 targeted therapy demonstrated robust anti-tumor effects both in vitro 3D biomimetic chip and in vivo mouse model, including angiogenesis inhibition, sorafenib sensitivity promotion and NK-cell cytotoxicity enhancement. Taken together, the microfluidic platform exhibited obvious advantages in mimicking functional characteristics of tumor microenvironments and developing targeted therapies.
A multisociety Delphi consensus statement on new fatty liver disease nomenclature
Authors: Mary E. Rinella, Jeffrey V. Lazarus, Vlad Ratziu, Sven M. Francque, Arun J. Sanyal, Fasiha Kanwal, Diana Romero, Manal F. Abdelmalek, Quentin M. Anstee, Juan Pablo Arab, Marco Arrese, Ramon Bataller, Ulrich Beuers, Jerome Boursier, Elisabetta Bugianesi, Christopher D. Byrne, Graciela E. Castro Narro, Abhijit Chowdhury, Helena Cortez-Pinto, Donna R. Cryer, Kenneth Cusi, Mohamed El-Kassas, Samuel Klein, Wayne Eskridge, Jiangao Fan, Samer Gawrieh, Cynthia D. Guy, Stephen A. Harrison, Seung Up Kim, Bart G. Koot, Marko Korenjak, Kris V. Kowdley, Florence Lacaille, Rohit Loomba, Robert Mitchell-Thain, Timothy R. Morgan, Elisabeth E. Powell, Michael Roden, Manuel Romero-Gómez, Marcelo Silva, Shivaram Prasad Singh, Silvia C. Sookoian, C. Wendy Spearman, Dina Tiniakos, Luca Valenti, Miriam B. Vos, Vincent Wai-Sun Wong, Stavra Xanthakos, Yusuf Yilmaz, Zobair Younossi, Ansley Hobbs, Marcela Villota-Rivas, Philip N. Newsome
Journal: Hepatology (2023)

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms “nonalcoholic” and “fatty” were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction–associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction–associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction–associated steatotic liver disease, who consume greater amounts of alcohol per week (140–350 g/wk and 210–420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.
Better Survival with Less Morbidity in Extremely Preterm Infants: Attacking the Heart of the Matter
Authors: Nimish V. Subhedar, Benjamin Frank, Steven H. Abman
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Better Survival with Less Morbidity in Extremely Preterm Infants: Attacking the Heart of the Matter ." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Chemokine receptor CXCR7 activates Aurora Kinase A and promotes neuroendocrine prostate cancer growth
Authors: Galina Gritsina, Ka-wing Fong, Xiaodong Lu, Zhuoyuan Lin, Wanqing Xie, Shivani Agarwal, Dong Lin, Gary E. Schiltz, Himisha Beltran, Eva Corey, Colm Morrissey, Yuzhuo Wang, Jonathan C. Zhao, Maha Hussain, Jindan Yu
Journal: Journal of Clinical Investigation (2023)

CXCR7 is an atypical chemokine receptor that recruits β-arrestin (ARRB2) and internalizes into clathrin-coated intracellular vesicles where the complex acts as a scaffold for cytoplasmic kinase assembly and signal transduction. Here, we report that CXCR7 was elevated in the majority of prostate cancer (PCa) cases with neuroendocrine features (NEPC). CXCR7 markedly induced mitotic spindle and cell cycle gene expression. Mechanistically, we identified Aurora Kinase A (AURKA), a key regulator of mitosis, as a novel target that was bound and activated by the CXCR7-ARRB2 complex. CXCR7 interacted with proteins associated with microtubules and golgi, and, as such, the CXCR7-ARRB2-containing vesicles trafficked along the microtubules to the pericentrosomal golgi apparatus, where the complex interacted with AURKA. Accordingly, CXCR7 promoted PCa cell proliferation and tumor growth, which was mitigated by AURKA inhibition. In summary, our study reveals a critical role of CXCR7-ARRB2 in interacting and activating AURKA, which can be targeted by AURKA inhibitors to benefit a subset of patients with NEPC.
E-cigarette Unit Sales by Product and Flavor Type, and Top-Selling Brands, United States, 2020–2022
Authors: Fatma Romeh M. Ali, Andrew B. Seidenberg, Elisha Crane, Elizabeth Seaman, Michael A. Tynan, Kristy Marynak
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

E-cigarette products, related policies, and use patterns change rapidly. In the United States, the prevalence of e-cigarette use is markedly higher among youths and young adults than it is among adults overall. In 2021, 4.5% of all adults aged ≥18 years (an estimated 11.1 million) and 11.0% of young adults aged 18-24 years (an estimated 3.1 million) currently (≥1 day during the previous 30 days) used e-cigarettes; during 2022, 14.1% of high school students (an estimated 2.14 million) currently used e-cigarettes (1,2). E-cigarettes often contain high concentrations of nicotine. Nicotine is highly addictive and can harm the adolescent brain, which continues to develop through approximately age 25 years (3). Since 2020, the availability of e-cigarette products has changed in response to multiple factors, including local and state policies to address flavored e-cigarette sales, actions undertaken by the Food and Drug Administration (FDA), COVID-19-related closures, and global supply chain disruptions. To assess trends in unit sales of e-cigarettes in the United States, by product and flavor, and top-selling brands, the CDC Foundation, Truth Initiative,* and CDC analyzed retail scanner data during January 26, 2020-December 25, 2022, from Information Resources, Inc. (IRI), a U.S. data analytics and market research company. Overall, unit sales increased by 46.6% during the study period. The unit share of menthol-flavored product sales remained relatively stable during this period, whereas nonmenthol flavor unit shares changed. During January 26, 2020-December 25, 2022, unit shares of tobacco-flavored and mint-flavored products decreased (from 28.4% to 20.1% and from 10.1% to 5.9%, respectively), whereas shares of other flavor sales increased (from 29.2% to 41.3%). In addition, during January 2020-December 2022, unit shares of prefilled cartridges decreased from 75.2% to 48.0%, and disposable e-cigarette unit share increased from 24.7% to 51.8% of total unit sales. The five top-selling e-cigarette brands for the 4-week period ending December 25, 2022, were Vuse, JUUL, Elf Bar, NJOY, and Breeze Smoke. Analysis of information on e-cigarette retail sales can guide strategies to prevent youth access to and use of e-cigarettes, including restrictions on flavored tobacco products (4).
Nav1.7 is essential for nociceptor action potentials in the mouse in a manner independent of endogenous opioids
Authors: Lunbin Deng, Michelle Dourado, Rebecca M. Reese, Kevin Huang, Shannon D. Shields, Kimberly L. Stark, James Maksymetz, Han Lin, Joshua S. Kaminker, Min Jung, Oded Foreman, Janet Tao, Hai Ngu, Victory Joseph, Meron Roose-Girma, Lucinda Tam, Susanne Lardell, Linnea Strid Orrhult, Paul Karila, Julien Allard, David H. Hackos
Journal: Neuron (2023)

Loss-of-function mutations in Nav1.7, a voltage-gated sodium channel, cause congenital insensitivity to pain (CIP) in humans, demonstrating that Nav1.7 is essential for the perception of pain. However, the mechanism by which loss of Nav1.7 results in insensitivity to pain is not entirely clear. It has been suggested that loss of Nav1.7 induces overexpression of enkephalin, an endogenous opioid receptor agonist, leading to opioid-dependent analgesia. Using behavioral pharmacology and single-cell RNA-seq analysis, we find that overexpression of enkephalin occurs only in cLTMR neurons, a subclass of sensory neurons involved in low-threshold touch detection, and that this overexpression does not play a role in the analgesia observed following genetic removal of Nav1.7. Furthermore, we demonstrate using laser speckle contrast imaging (LSCI) and in vivo electrophysiology that Nav1.7 function is required for the initiation of C-fiber action potentials (APs), which explains the observed insensitivity to pain following genetic removal or inhibition of Nav1.7.